Abstract: The invention is directed to three-dimensional, engineered, bioprinted biological tissue constructs exhibiting a liver disorder, methods of making the constructs, and use of the constructs in assays, such as drug testing and molecular diagnostic testing, including methods of assessing the ability of a candidate therapeutic agent to reverse, reduce, or prevent a liver disorder, and methods for biomarker discovery.

Abstract: Siglec-8 antibodies and uses thereof are described. The Siglec-8 antibodies can be fully human and can be used for a variety of purposes, including in the research, diagnosis, and treatment of eosinophil and mast cell related disorders, such as asthma, rhinitis, dermatitis, eosinophilic gastrointestinal disorders, eosinophilic pneumonia, anaphylaxis, urticaria, eosinophilic cellulitis and fasciitis, Churg-Strauss syndrome, hematologic malignancies involving eosinophils or mast cells, and mastocytosis.

Abstract: Anti-CD33 antibodies are described. The anti-CD33 antibodies can bind within the V-set Ig-like domain or the C2-set Ig-like domain of CD33. Epitopes on the C2-set Ig-like domain can provide a “pan-binding” site, to which the cognate antibody will bind regardless of whether the CD33 molecule also contains the V-set domain (as in, for example, CD33FL) or not (as in, for example, CD33?E2). Alternative epitopes on the C2-set Ig-like domain are accessible for binding if the V-set domain is absent (e.g., as in CD33?E2). Antibodies that bind an epitope on the C2-set Ig-like domain (whether they exhibit pan or V-set absent binding) are directed at novel therapeutic targets and can increase therapeutic efficacy against CD33-related disorders. Also described are molecules comprising a binding-competent domain from at least one described anti-CD33 antibody, including scFvs, bi-specific antibody molecules, chimeric antigen receptors, and immunoconjugates. Methods of use are also provided.

Abstract: Anti-CD33 antibodies are described. The anti-CD33 antibodies can bind within the V-set Ig-like domain or the C2-set Ig-like domain of CD33. Epitopes FIG. 1A on the C2-set Ig-like domain can provide a “pan-binding” site, to which the cognate antibody will bind regardless of whether the CD33 molecule also contains the V-set domain (as in, for example, CD33FL) or not (as in, for example, CD33?E2). Alternative epitopes on the C2-set Ig-like domain are accessible for binding if the V-set domain is absent (e.g., as in CD33?E2). Antibodies that bind an epitope on the C2-set Ig-like domain (whether they exhibit pan or V-set absent binding) are directed at novel therapeutic targets can increase therapeutic efficacy against CD-33-related disorders. Also described are molecules comprising a binding-competent domain from at least one described anti-CD33 antibody, including scFvs, bi-specific antibody molecules, chimeric antigen receptors, and immunoconjugates. Methods of use are also provided.

Abstract: A medical system comprises an elongate device, an elongate sheath configured to extend within the elongate device, and an imaging probe configured to extend within the elongate sheath. The elongate sheath includes an identification feature. The medical system further comprises a control system configured to receive imaging data from the imaging probe. The imaging data is captured by the imaging probe. The control system is further configured to analyze the imaging data to identify an appearance of the identification feature within the imaging data. The control system is further configured to, based on the appearance of the identification feature, register the imaging data to a reference frame of the elongate device.

Abstract: A method for controlling fluid delivery to a medical instrument comprises releasing, from a reservoir of a known size and having fluid at a volume and a first fluid pressure, a released fluid volume of the fluid to the medical instrument. The method also comprises measuring a vented fluid volume and determining a discharged fluid volume through the medical instrument based on the released fluid volume and the vented fluid volume.

Abstract: Humanized, chimeric, murine, and human antibody or antigen binding derivatives thereof that bind to an extracellular domain of interleukin-3 (IL-3) receptor ?-chain (CD123) anti-CD123 monoclonal antibodies are provided. Nucleic acids encoding the antibody or antigen binding derivative thereof that binds to an extracellular domain of interleukin-3 (IL-3) receptor ?-chain (CD123) and expression vectors comprising the nucleic acid are also provided. Bispecific affinity reagents comprising a first binding domain that specifically binds to an extracellular domain of interleukin-3 (IL-3) receptor ?-chain (CD123); and a second binding domain that specifically binds to a therapeutic payload and uses thereof are provided. Embodiments of the invention include isolated antibodies and derivatives and fragments thereof, pharmaceutical formulations comprising one or more of the humanized, chimeric, or human anti-CD123 monoclonal antibodies; and cell lines that produce these monoclonal antibodies.

Abstract: Chimeric antigen receptors (CARs) with binding domains derived from a novel suite of human CD33-binding antibodies are described. The CARs include optimized short and intermediate spacer regions. The current disclosure also provides methods of cell expansion/activation processes utilizing IL-2, IL-7, IL-15, and/or IL-21 that improve cellular proliferation and cell lysis of the CARs as described.

Abstract: A suite of novel anti-CD33 antibodies is described. The provided antibodies are pan-binders, binding the C2-set Ig-like domain in the presence or absence of the V-set Ig-like domain of CD33; are C2-set specific binders, binding the C2-set Ig-like domain only in the absence of the V-set Ig-like domain of CD33; or are V-set binders, binding the V-set Ig-like domain of CD33. The antibodies provide novel therapeutic and diagnostic tools against CD33-related disorders, such as acute myeloid leukemia (AML).

Abstract: Chimeric antigen receptors (CARs) with binding domains derived from a novel suite of CD33-binding antibodies are described. The CARs include optimized short and intermediate spacer regions. The current disclosure also provides methods of cell expansion/activation processes utilizing IL-2, IL-7, IL-15, and/or IL-21 that improve cellular proliferation and cell lysis of the CARs as described.

Abstract: A suite of novel human anti-CD33 antibodies is described. The provided antibodies are pan-binders, binding the C2-set Ig-like domain in the presence or absence of the V-set Ig-like domain of CD33 or are V-set binders, binding the V-set Ig-like domain of CD33. The antibodies provide novel therapeutic and diagnostic tools against CD33-related disorders, such as acute myeloid leukemia (AML).

Abstract: Systems and methods to selectively protect therapeutic cells by reducing CD33 expression in the therapeutic cells using base editors and targeting non-therapeutic cells with an anti-CD33 therapy are described. The selective protection results in the enrichment of the therapeutic cells while simultaneously targeting any diseased, malignant and/or non-therapeutic CD33 expressing cells within a subject.

Abstract: Systems and methods for integrated real-time visualization while performing a minimally invasive procedure within anatomic passageways include a flexible catheter having one or more first lumens and a first positioning system, an imaging probe having one or more imaging elements, and a scaling device. In souse embodiments, the scaling device includes a plurality of second lumens and the flexible catheter and the imaging probe are each optionally deployed through a respective one of the second lumens. In some embodiments, the one or more imaging elements include one or more ultrasound transducers. In some embodiments, the scaling device seals the anatomic passageways at a scaling location using one or more balloons, and the anatomic passageways distal to the sealing location are collapsed. In some embodiments, the first positioning system includes one or more position sensors. In some embodiments, the procedure is performed after the passageways are collapsed.

Abstract: Systems and methods to selectively protect therapeutic cells by reducing CD33 expression in the therapeutic cells and targeting non-therapeutic cells with an anti-CD33 therapy. The selective protection results in the enrichment of the therapeutic cells while simultaneously targeting any diseased, malignant and/or non-therapeutic CD33 expressing cells within a subject.

Abstract: A medical system includes a flexible catheter, an imaging probe, a working catheter, and a positioning system. The flexible catheter includes a plurality of first lumens and a sealing device having one or more balloons to seal the anatomic passageways at a sealing location and one or more flaps or valves to remove air from the anatomic passageways. The imaging probe and working catheter are receivable within the plurality of first lumens and extend through the sealing device. The working catheter includes one or more second lumens to receive a medical instrument. The positioning system is configured to determine a position of a distal portion of the flexible catheter, the imaging probe, or the working catheter. The medical system is configured to collapse a portion of the anatomic passageways distal of the sealing location by removing air from the anatomic passageways to facilitate ultrasound imaging using the imaging probe.

Abstract: The present invention provides a combination epigenetic factors and bispecific compounds targeting CD33 and CD3 in the treatment of myeloid leukemia, wherein the epigenetic factor is selected from the group consisting of histone deacetylase (HDAC) inhibitors, DNA methyltransferase (DNMT) I inhibitors, hydroxyurea, Granulocyte-Colony Stimulating Factor (G-CSF), histone demethylase inhibitors and ATRA (All Trans-retinoic acid). Accordingly, the invention provides a pharmaceutical composition comprising a CD33 targeting compound and at least one epigenetic factor and an epigenetic factor for use in the amelioration and/or treatment of a myeloid leukemia, wherein the epigenetic factor increases the responsiveness of a patient to a CD33 targeting compound.

Abstract: A method for controlling fluid delivery to a catheter comprises charging a reservoir, of a known size, with a fluid to a volume at an initial fluid pressure and releasing a released fluid volume of the fluid from the reservoir to the catheter. The method also comprises measuring a vented fluid volume and determining a discharged fluid volume through the catheter based on the released fluid volume and the vented fluid volume.

Abstract: Flexible elongate device systems and methods include a flexible elongate device having a flexible body and an axial support structure. The axial support structure includes at least one groove extending along a length of the axial support structure. The flexible elongate device further includes a plurality of control elements for actuating the flexible elongate device. Each of the plurality of control elements extends through one of the at least one groove of the axial support structure. In some embodiments, the at least one groove includes a plurality of grooves spaced circumferentially around the axial support structure. In some embodiments, the flexible body includes lumens that extend through the at least one of the grooves. The control elements are disposed in the lumens. In some embodiments, the flexible body includes a main lumen that extends centrally through the flexible body. The main lumen provides a channel for a medical tool.

Abstract: Anti-CD33 antibodies are described. The anti-CD33 antibodies can bind within the V-set Ig-like domain or the C2-set Ig-like domain of CD33. Epitopes on the C2-set Ig-like domain can provide a “pan-binding” site, to which the cognate antibody will bind regardless of whether the CD33 molecule also contains the V-set domain (as in, for example, CD33FL) or not (as in, for example, CD33?E2). Alternative epitopes on the C2-set Ig-like domain are accessible for binding if the V-set domain is absent (e.g., as in CD33?E2). Antibodies that bind an epitope on the C2-set Ig-like domain (whether they exhibit pan or V-set absent binding) are directed at novel therapeutic targets and can increase therapeutic efficacy against CD33-related disorders. Also described are molecules comprising a binding-competent domain from at least one described anti-CD33 antibody, including scFvs, bi-specific antibody molecules, chimeric antigen receptors, and immunoconjugates. Methods of use are also provided.

Abstract: A method for solving the NP complete problem 3SAT and other computational problems which can be reduced to it. Quantum mechanical operations are performed on a finite number of quantum mechanical bits, or “qubits,” in such a way as to concentrate probability in states which solve a given 3SAT problem, provided they exist. Concentration of probability is achieved by generalizing the traditional, reversible model of quantum computation to include irreversible operations mapping one density matrix to another.